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Prevention of infectious diseases through inhibition of bacterial adherence to host tissues.

Research Project

Project/Area Number 16390540
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionThe University of Tokushima (2005)
Kagoshima University (2004)

Principal Investigator

ITO Hiro-O  The University of Tokushima, Institute of Health Bioscience, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (40213079)

Co-Investigator(Kenkyū-buntansha) SOUTOME Sakiko  Kagoshima University, Hospital, Research Associate, 医学部・歯学部附属病院, 助手 (20325799)
軒原 清史  (株)ハイペップ研究所, 最高科学責任者・CEO (60137073)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
KeywordsPeptide Libraries / Decombolution / Oral Bacteria / Infective Endocarditis / Positional Scanning / Monoclonal Antibodies / Fibronectin / Natural Product Libraries / デコンボルーション
Research Abstract

Infective endocarditis is often caused by passage of oral endogenous bacteria into the blood stream. Such bacteremia occurs after tooth extraction, and occasionally even after brushing of the teeth. Abnormal or damaged heart valves, including artificial valves, show high risk of infection. Antibiotics are widely used to prevent this infection, however, frequent use of these have resulted in the generation of resistant mutants, which generate serious social problems. Thus, the development of more effective and safer drugs for the prevention of such infections is very desirable. The adhesion of bacteria to fibronectin, one of the major extracellular matrix protein exposed on the wound endocardia, is considered critical for the infection. We have previously found a novel mode of interaction between endocarditis-causing bacteria and human fibronectin. The present study focuses on the discovery of candidate compounds that inhibit the association between microorganisms and fibronectin. Positional scanning libraries (PSL) with N-terminal biotinylated 6-mer peptides have been constructed and screened for binding to a monoclonal antibody for fibronectin that inhibits the bacterial fibronectin-binding. The consensus sequences derived from these experiments are expected to be structural mimetics of the local structure of fibronectin involved in the bacterial adhesion. Since individual synthetic 6-mer peptides did not show the desired action, discontinuous epitopes can be envisaged and therefore a 9-mer-PSL was constructed to reveal conformational epitopes. In the second Library, several 9-mer peptides based on the screening were synthesized and gave improved results.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (8 results)

All 2006 2005 2004 Other

All Journal Article (8 results)

  • [Journal Article] Screening of Peptides that Inhibit Bacterial Binding to Fibronectin Using Combinatorial Peptide Libraries.2006

    • Author(s)
      Ito, H.-1.
    • Journal Title

      Int. J. Pep. Res. Ther. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Screening of Peptides that Inhibit Bacterial Binding to Fibronectin using Combinatorial Peptide Libraries.2006

    • Author(s)
      Ito, H. -O.
    • Journal Title

      Int.J.Pep.Res.Ther. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Screening of Inhibitor for Bacterial Binding Using Positional Scanning Combinatorial Libraries with Two Different Peptide Length.2005

    • Author(s)
      Ito, H.-0.
    • Journal Title

      Abstract Book of the 6th Australian Peptide Conference

      Pages: 60-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Screening of Inhibitor for Bacterial Binding Using Positional Scanning Combinatorial Libraries with Two Different Peptide Length.2005

    • Author(s)
      Ito, H.-O.
    • Journal Title

      Abstract Book of the 6th Australian Peptide Conference

      Pages: 60-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Screening of Inhibitor for Bacterial Binding Using Positional Scanning Combinatorial Libraries with Two Different Peptide Length.2005

    • Author(s)
      Ito, H. -O.
    • Journal Title

      Abstract Book of the 6th Australian Peptide Conference

      Pages: 60-60

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Induction of immune response to Streptococcus pneumoniae by administration of oral viridans streptococci via phosphorylcholine determinant.2005

    • Author(s)
      Miwa, Y. et al.
    • Journal Title

      FEMS Immunol.Med.Microbiol. : (2005) 43(3)

      Pages: 441-448

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification and characterization of bacterial-binding property in the type III repeat domain of fibronectin.2004

    • Author(s)
      Ito, H.-O.et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 320(2)

      Pages: 347-353

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Screening of Peptides that Inhibit Bacterial Binding to Fibronectin Using Combinatorial Peptide Libraries.

    • Author(s)
      Ito, H.-O.
    • Journal Title

      Int.J.Pep.Res.Ther. (manuscript in submission)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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